Download Fertility Options for Single Women,Fertility

Fertility Options for Single
Women
Fertility Options for Single Women
Single women may face some challenges regarding fertility
options: understanding them then picking one or more options,
suitable for your reproductive plans. Clearly, a woman cannot
delay pregnancy indefinitely, as the number of good quality
eggs decline quickly in her 30s and older.
Decline in Fertility with age
Modern reproductive medicine enables single women to be
mothers now and in the future. As with anything in
reproduction, the younger you are, the more successful your
efforts will ultimately be, irrespective of your choices. In
addition, think of what would you accept: donor sperm? are you
ready to get pregnant now or do you want do that in the
future?
Are you ready to Start a Family without a Partner?
This could be a difficult question considering the time,
financial and emotional commitment of raising children without
a male partner. A psychologist with expertise in reproductive
issues can help women tackle issues as readiness and
commitment, disclosure to children when mature, capitalizing
on family resources, legal issues and many more. Some
anonymous donors accept open identity in the future.
Starting a family without a male partner requires a selection
of sperm donor. The sperm donor could be anonymous (from a
sperm bank) or known (friend). In either cases, the donor is
screened for infectious diseases (hepatitis B, hepatitis C,
HIV, Syphilis, Gonorrhea and Chlamydia) and common genetic
abnormalities. The sperm is quarantined then the donor is
retested for infectious diseases. Tests are done in a
specialized high accuracy labs.
How to use donor sperm to achieve a pregnancy?
This is a question related to female ovarian reserve and other
fertility factors. If the fallopian tubes are open, as
indicated by HSG (hysterosalpingogram, X-ray of the tubes)
then IUI (intrauterine insemination) is possible. Age is also
an important factor. Women 38 or older have much higher chance
of conceiving with IVF than IUI using frozen sperm. This issue
require thorough evaluation by a reproductive endocrinologist.
On Starting a Family with a Partner in the Future
If the use of donor sperm is not acceptable, egg freezing is a
viable option for women with reasonable ovarian reserve and
younger than 40. Evaluation of antral follicle count using
vaginal ultrasound and antimullerian hormone levels (AMH) can
predict response to fertility medications and ultimate egg
yield from the cycle. Age reflects well how many of these eggs
are chromosomally normal. The ovaries are stimulated using
injection medications. Eggs are retrieved under vaginal
ultrasound guidance which is a minor procedure. Mature eggs
are frozen 4 hours later using vitrification. Immature eggs
are cultured for <24 hours and frozen if mature. The eggs can
be stored for years to come.
If the number of eggs retrieved is low another egg freezing
cycle can be attempted to freeze more eggs.
When pregnancy is desired the eggs are thawed and fertilized
via ICSI (direct injection of the sperm into the egg) and the
resulting embryos are transferred into the uterus after
preparation of its lining. The pregnancy rate after egg
freezing is close to fresh eggs and is age dependent.
These options allow single women achieve their reproductive
goals while respecting their values and preferences.
Fertility Treatment: Do not
be Distracted
Fertility Treatment: do not be distracted by worthless
recommendation
Fertility Treatment:
Distracted
Do
not
be
When contemplating options for fertility treatment with your
own eggs, it always boils down to continue frequent
intercourse, ovarian stimulation / ovulation induction + IUI
or some form of IVF. During consultation or when weighing your
options do not lose perspective of the big picture. Many
suggestions may present themselves and serve to distract you.
Men and Women load up on these distractions from the web,
friends, primary care physicians or the couple themselves.
Some of these recommendations are harmful because they shift
the focus to non-proven interventions and most notably cause
delay consultations with a reproductive endocrinologist and
completing the infertility workup or starting treatment if
needed.
Do not be distracted by these arguments
I am Healthy
Many women in America consider being healthy as being fertile.
The media also bombard us with photos of beautiful women in
their forties with babies. Truly many women, are in great
shape with ideal body weight, exercise regularly, have no
medical problems and feel great about themselves.
Fertility though speaks to a specific set of factors related
to the ovaries, fallopian tubes and quality of sperm. Healthy
women can have low egg reserve or blocked fallopian tubes or
their partners have low sperm counts. Hence their fertility
could be impaired. On the other hand, women not leading a
healthy lifestyle or having a medical disorder can be very
fertile if all fertility factors (tube, ovary, sperm) are
functional.
I did not try enough
If you do not use birth control pills or condoms and you have
having regular intercourse, then you are trying, irrespective
of your conscious intentions. If you are you had regular
intercourse for one year and are younger than 35 years or six
months and 35 or older, then you have tried. Regular
intercourse means two to three times a week. If you had
intercourse with reasonable frequency for 6months to a year
and you are not pregnant consult with a fertility specialist.
There is a strong relationship between the length of trying
and pregnancy rate. The longer that you have been trying, the
lower the chance for spontaneous conception.
I did not time my ovulation
Timing your ovulation is not required at all if you are trying
to conceive. Actually timing your ovulation maybe harmful to
your chance to conceive. Because the methods you would use to
time ovulation (cervical mucus, ovulation prediction kits,
basal body temperature or intelligent thermometers and apps)
are not accurate, you may miss valuable time and have
intercourse at the wrong time if ovulation takes place
unexpectedly early. Moreover, you cannot get higher odds for
getting pregnant above and beyond having intercourse three
times a week because sperm will be available all the time when
you ovulate. Several studies failed to show any increase in
pregnancy rates using many of these timing methods.
On Fertility Apps and other monitors
Many (>4 million) websites discuss times intercourse utilizing
other methods (fertility monitor, cervical mucus, calendar
methods, urine LH kits..). More recently technology
entrepreneurs are delved into the “trying to conceive” area
and volunteered advice. There is no evidence to support that
any calculation method improves the odds of getting pregnant
over frequent intercourse. These non-scientific advice is a
major distraction. Even if these apps collected data on how
many women got pregnant, without a comparison group, is not a
prove that they actually work. One study indicated that timed
intercourse is associated with higher incidence of erectile
dysfunction (43%) and extramarital sex (11%).
My progesterone level is not optimal
For almost all women, low progesterone level is not a cause
for infertility. In natural cycles, progesterone starts to
rise after ovulation. Levels of 3 nanogram/mL or more
indicates ovulation, Optimal levels to maintain the lining of
the uterus are 8 to 10ng/mL. Levels less than 8 (luteal phase
defect) may lead to miscarriage because progesterone is not
adequate to maintain the lining of the uterus but it is not a
cause for not getting pregnant (infertility). Progesterone is
monitored, and supplemented if low, during fertility treatment
but in itself low progesterone is not a cause for infertility.
On Clomid & Letrozole
Clomiphene is widely used as initial fertility treatment. This
use is commonly not appropriate because
a. clomid is used without infertility workup (checking ovarian
reserve, sperm analysis and fallopian tubes)
b. clomid
is used without performing basic tests related to
the safety of getting pregnant (infectious disease and genetic
screening)
c. clomid is used by women that are not likely to benefit from
it e.g regularly ovulating women with low ovarian reserve and
unexplained infertility. Women that are most likely to benefit
from clomid are women with chronic anovulation e.g women with
polycystic ovary syndrome (PCOS).
d. clomid is commonly used with no monitoring using
ultrasound. If you do not get pregnant, one would not know if
you did ovulate or not. 10-20% of women do not respond to
clomid. If you are destined to get pregnant, there is a
possibility that you have many eggs developing in the ovary
because you are unduly sensitive to the medicine. Strong
response to clomid makes you at risk for multiple pregnancy
e. clomid is commonly use for extended periods of time while
the majority of pregnancies take place in the first 3 months.
f. IUI is preferred to intercourse only, in clomid cycles
because it can cause the cervical mucus to be thick. IUI
bypasses the cervical mucus and deposit the sperm into the
cavity of the uterus
g. Letrozole is similar to clomid regarding the use and
indication but there is evidence that pregnancy is higher
after letrozole compared to clomid.
Use clomid or better ltrozole for the right indication, with
monitoring and for 3 (max 6) months only.
On Setting Time Limits
For each fertility treatment step: intercourse, ovarian
stimulation + IUI or IVF define the number of cycles you will
try before proceeding to the next step. Statistically, these
treatments are more likely to succeed in the first three
treatment attempts. Subsequently, the chance for getting
pregnant diminishes and you and your physician should consider
moving to another treatment.
Do not loose track
ovarian reserve
of
your
age
and
You have normal fallopian tubes and partner sperm and you
ovulate every month. Younger women are encouraged to try (have
regular intercourse). The duration of trying on your own
should be guided by ovarian reserve tests and age. Younger
women with good reserve can try a bit longer than older women
or women with low reserve. This recommendation should be based
on scientific information not general perception. Do not
accept the advice ‘ keep trying’ from any one without
considering you age and without performing the tests for
ovarian reserve (vaginal ultrasound, AMH and FSH on day 3).
Female age is the most important factor in occurrence of a
healthy pregnancy and should be the prime consideration even
if ovarian reserve tests and other factors are normal.
There is a plethora of low quality information, recommendation
and advice out there. Women accumulate them from multiple
sources or just using there simple logic. They can lead to
delay in fertility testing and fertility treatment that could
be detrimental to future fertility.
Pre-implantation
Genetic
Screening (PGS): What are we
really talking about?
Pre-implantation Genetic Screening
(PGS): What are we really talking
about?
The tenant behind pre-implantation genetic screening (PGS) is
to biopsy one or few cells from each embryo after creation,
analyze the chromosomes for each embryo and transfer the ones
that has normal chromosomes back into the uterus to boost IVF
success and increase the live birth rate.
Central to this idea is that abnormal chromosomes in the
embryos is the main reason why an embryo does not yield a
newborn. It is logic then that PGS should allow the selection
for the best embryo (preferably one only) for transfer into
the uterus ending into one singleton newborn.
If this premise is accepted then the following assumptions
should also be generally accepted
a. All or the majority of embryos reached the appropriate
stage of development and expansion to allow biopsy.
b. Biopsy of the embryo does not harm its ability to implant
c. The cell or few cells obtained represent the rest of the
embryo (has identical chromosomes to all the other cells in
the embryo)
d. The platform used to analyze the embryo chromosomes is
close to 100% accurate (otherwise some embryos will be wasted
because they are abnormal according to the test, while they
are actually normal). The platform reports only the
chromosomes of the embryo and is not accountable for other
elements of implantation i.e. the endometrium.
e. The delay (one or more days) needed to finish the testing
does not affect embryo implantation
f. Freezing and then thawing of a biopsied embryo does not
affect its implantation potential
g. Patients and physicians have agreed on how to calculate
success: how many live births one would obtain from all
embryos resulting from a single IVF cycle (all fresh and
frozen embryos) i.e. total potential of one IVF cycle versus
fresh embryo transfer only.
h. The added cost of biopsy and testing of embryos, potential
increases the delivery rate and reduces the incidence of
multiple pregnancy and miscarriage is cost-effective from the
viewpoint of individual and a modern society.
The initial attempt to perform Preimplantation genetic
diagnosis using an old technology called FISH that tested 7 to
9 chromosomes proved harmful few years ago and that its wide
adoption at that time was a form of medical illiteracy :
because it depends on logic not actual well conducted study.
When the studies were conducted, they all showed that women
universally achieved lower pregnancy rates after PGS.
New platforms are now available to test for all the
chromosomes (array cGH and SNP array) and using cells
(trophoectoderm) obtained from more advanced stages of the
embryo (blastocyst). The question in hand is should we adopt
these techniques, not as a research tool, but as the standard
of care that should be offered to the majority of women
undergoing IVF?
How Effective is PGS? The case for
Logic
Applying logical thinking to modern pre-implantation genetic
screening (PGS) methods indicates:
a. Not all embryos will reach the blastocyst stage (day 5) to
be suitable for biopsy. Not all physicians and patients push
their embryos to the blastocyst stage especially if few
embryos exist in culture on day 3. Moreover, some normal
embryos may not survive extended culture to blastocyst.
b. There are no conclusive evidence that biopsy of the
trophoectoderm (the part that makes the placenta) of an embryo
does not harm the embryo.
c. Mosaicism ; when one or few cells are different in
chromosomes than the rest of the cells, is known to take place
in embryos. The cells in the trophoectoderm maybe abnormal
while the cells in the embryo maybe normal. Interestingly the
embryo can later get rid of the abnormal cells in the
trophoectoderm. This can lead in misdiagnosis of the embryo as
abnormal while the embryo itself has the potential to implant
and yield a healthy baby.
d. The platform used to analyze the embryo chromosomes is not
100% accurate either because of the accuracy of the test
itself or because of mosaicism. The accuracy reported by labs
administering the test is 97%. This means some normal embryos
will be discarded and some abnormal embryos will be
transferred. Actually the accuracy was not validated by many
labs, only very few worldwide. Clinically some physicians have
experienced much lower accuracy (80 or 90%). The platform
reports only the chromosomes of the embryo and is not
accountable for other elements of implantation i.e. the
endometrium. So it is possible that the lower accuracy is due
to other elements on embryo gentics (other than the number of
chromosomes) or the lining of the uterus.
e. Currently the transfer of embryos into the uterus has to be
delayed for one day (day 6) or several weeks (embryo has to be
frozen then thawed back after results are obtained). This
delay may reduce implantation of the embryo because it will
not match the window of implantation in the lining of the
uterus. This is a controversial point as some researchers
found no difference in implantation between day 5 and day 6.
This research, however, is not widely replicated.
f. After PGS some ‘normal’ embryos will be frozen. The
survival of thawed and biopsied embryos is maybe reduced,
potentially leading to loss of normal embryos. No large
studies on survival of biopsied embryos after thaw exist.
g. Patients and physicians have agreed on how to calculate
success: if success is calculated based on how many live
births one would obtain from all embryos resulting from a
single IVF cycle (fresh and frozen) i.e. total potential of
one IVF cycle, then PGD has no value as it will not make an
abnormal embryo normal or vice versa. If the success is based
on what happens in the fresh cycle only with no regard to
frozen embryos then PGS may improve the success rate of IVF.
All assuming an excellent embryo freezing program.
For exampe If you are a young woman <38, with a good number of
available embryo on day 5, say 4 blastocysts that are suitable
for biopsy, you may elect to
i. transfer one embryo in the fresh cycle and freeze 3
embryos. If you are not pregnant, then transfer one embryo in
each subsequent frozen cycle. If you are destined to get
pregnant you will do that within a maximum of 3 months after
your initial IVF and the risk for multiple pregnancy is
minimized to 1% or less. If you were not destined to get
pregnant no testing would have helped you or
ii. Alternatively, you may elect to test all your embryos in
the fresh cycle, transfer one normal embryo, if any and freeze
any normal embryo remaining. The potential benefit is getting
pregnant in the fresh cycle instead of getting pregnant 1-3
months later. Also you will reduce the risk of miscarriage
because abnormal embryos will likely be eliminated. The
potential risks are misdiagnosis by PGS (not 100% accurate),
loss of a thawed embryo (did not survive biopsy and freeze)
and lower implantation potential of a normal embryo due to
biopsy and delayed transfer.
h. A cost-effective analysis for PGS is not available at this
time. The added costs are biopsy and testing of embryos. The
potential benefits are increase in the delivery rate and
reduction in multiple pregnancy and miscarriage. In the
scenario above you either pay for i. frozen embryo transfer(s)
if you do not get pregnant in the fresh cycle or ii. pay for
ICSI (required for PGS by the majority of programs), biopsy
and testing in the fresh cycle and frozen embryo transfer(s)
if you do not get pregnant in the fresh cycle. In terms of
multiple pregnancy, it can be minimized in either pathways if
your physician is transfers one embryo anyway, tested or not.
Things are not that simple, the payer will also make a
difference: PGS is completely out of a patient pocket as it is
not covered by any insurance while frozen embryo transfer may
or may not be covered.
How Effective is PGS? The case for
Published Studies
In general decision making in biological sciences is not
amenable to logic, but determined by well designed ad well
conducted studies. So far, three studies were published using
the new platforms for embryo chromosome analysis, aiming at
increasing IVF success. The studies were criticized because of
1. Restricted to young women (median age 31 to 32) so results
cannot be generalized to the general IVF population: 2 studies
2. Did not account for frozen embryos: all studies
3. The studies did not demonstrate superiority of PGS to
transfer best embryos based on morphology (shape): one study.
Specifically a transfer of a tested embryo in the fresh cycle
was not inferior to transfer of two untested embryos. Non
inferiority does not mean superiority. Noninferiority study
design is not suitable for a PGS study as patients and
physicians are only interested in such an expensive treatment
that can harm their embryos only if it promises superior
results for their infertility treatment. Moreover, treatment
could actually be inferior because a limit is placed that will
make the outcome non inferior, in that study 20%. So if the
difference is less than 20% PGS is considered not inferior.
4. End point should be live birth or ongoing pregnancy.
Surrogate or intermediate endpoints as pregnancy, implantation
(short of a baby in hand or at least pregnancy beyond 20
weeks) are not ideal outcomes.
Randomized studies related to pre-implantation genetic
testing using newer platforms were independently analyzed. So
far no study showed that PGS is superior to the strategy of
transferring the best embryo based on morphology (the standard
of care). Moreover due to factors related to the biology of
reproduction and that the accuracy of the test is unlikely to
reach 100% accuracy soon, it is unlikely that PGS will prove
beneficial to women undergoing IVF for fertility treatment.
PGS may only shorten the time to pregnancy but will not be
able to improve the pregnancy rate and due to inaccuracies may
even reduce it.
Alternatives to PGS are being studied. One alternative is time
lapse photography of the embryos to observe the cell division
of the embryo cells and select the best embryo for transfer.
It is noninvasive but further studies are required before its
ready for general use. Another alternative is polar body
biopsy of oocytes but results of ongoing studies are not
available yet.
It is possible that factors in this article could be
interpreted differently in a specific situation by patients
and their physicians, in conjunction with the number of mature
eggs produced, but it does not appear that PGS is ready for
generalized application in the majority of IVF population.
Fertility Treatment Options
Fertility Treatment Options: What Are Infertility Treatments?
Following detailed fertility investigation of the male tubal
and ovarian factors, patient and her reproductive
endocrinologist decide together on the optimal fertility
treatment options.
Factors to consider in selecting the best fertility treatment
options include:
Sperm source
1. Is there a male partner: if so what is the ejaculate
volume, sperm concentration, motility and shape? if >10
million moving sperm then pregnancy through intercourse
or IUI is possible. Lower numbers indicates IVF or ICSI.
If azospermia (no sperm in the ejaculate) then surgical
sperm retrieval may be needed (TESE) or donor sperm can
be used.
2. If there is no male partner: anonymous or known donor
sperm is used
Tubal Factor
1. Open fallopian tubes allow for natural conception or
IUI.
2. Blocked fallopian tubes require IVF. Sometimes tubes can
be fixed using tubal surgery.
3. Blocked and dilated fallopian tubes (Hydrosalpinx)
require surgical removal of the dilated tubes followed
by IVF. Dilated tubes are very difficult to fix and can
leak fluid into the uterine cavity and prevent
implantation of the embryo.
Ovarian Factor
1. Women who do not ovulate due to polycystic ovary
syndrome (PCOS): ovulation can be induced using oral
medications (clomid or letrozole) or injection
medications (gonadotropins). This is usually combined
with IUI.
2. Women who do not ovulate due to defect in the master
gland in the brain (Hypothalamic amenorrhea): ovulation
can be induced using injection medications
(gonadotropins). This is usually combined with IUI.
3. Women diminished ovarian reserve and unexplained
(idiopathic) infertility commonly have lower quality
eggs and may benefit from inducing multiple ovulation
followed by IUI or IVF, to increase the chance that one
of the eggs is healthy (chromosomally normal).
Donor Eggs
1. Donor eggs are needed in women with low egg reserve that
fail multiple IVF cycles after menopause or those who
carry some genetic abnormalities.
2. Donor eggs can enable same sex male couples parent a
child (together with a gestational carrier).
Gestational carriers
1. Gestational carriers enable women to parent a child if
the uterus is absent or was removed due to a disease e.g
endometrial cancer or if the lining of the uterus is
damaged e.g
scrapping.
intrauterine
scarring
due
to
prior
2. Gestational carrier enable women who cannot get pregnant
to parent a child e.g history of breast cancer
3. Gestational carriers enable same sex male couples to
parent a child.
Genetic analysis of the eggs or embryos (PGD)
1. Women and men with risk of conceiving a child with a
specific genetic disorder e.g cystic fibrosis, sickle
cell anemia should consider testing their embryos before
transfer into the uterus (PGD)
2. PGD can also be used for selecting the sex of the baby
for family balancing.
3. PGD can be used to test the chromosomes of the embryo to
increase the chance for pregnancy in women select women
but its efficacy for that purpose is still being
investigated.
Fertility Preservation
1. Women at risk for diminished fertility due to a medical
problem or treatment e.g breast cancer can freeze their
eggs or embryos to use later
2. Men at risk for azospermia due to genetic factors,
cancer and cancer treatment can freeze sperm for use
later
3. Many other techniques for fertility preservation can
also be applied to adults and children to preserve
reproductive organs and tissue.
Many fertility treatment choices exist to help women and men
conceive a child. One or more of these methods can be tailored
to each
i. individual circumstances:
singles women or men,
heterosexual couples or
same sex couples.
ii. reproductive aim:
wants to get pregnant now versus later,
wants one child only or accepts twins,
wants to conceive a child of certain sex,
will use own uterus or a gestational carrier,
will use own gametes- sperm or egg or donor gametes.
To learn more about
nycivf.org
Thin
fertility treatment options please visit
Endometrial
Lining
During Fertility Treatment
Some women encounter thin endometrial lining and abnormal
pattern during natural cycles or during fertility treatment.
The implantation of embryos is impaired in women with thin
lining and abnormal pattern. Abnormal lining can lead to
recurrent implantation failure in young women undergoing IVF
after repeated transfer of good quality embryos.
The thickness of the lining appropriate for implantation is
commonly defined at 7 to 13mm measured on vaginal ultrasound.
The most receptive pattern of the lining of the uterus is a
tri-laminar pattern (three line pattern) without little
homogenous pattern when visualized shortly before ovulation
(pattern 1 and 2 of the photo, Fanchin et al 2000).
Causes for Abnormal Endometrial lining
during Fertility Treatment
The two most common abnormalities encountered are
a. Fluid inside the Cavity: fluid may accumulate inside the
cavity due to stenosis (narrowing) of the cervix probably
because of prior surgery or leak of fluid from a blocked
dilted fallopian tube (hydrosalpinx).
b. Thin lining and /or abnormal pattern of endometrium.
Possible causes
1. Acquired (Asherman Syndrome): prior D&C (termination of
pregnancy), uterin surgery (e.g fibroid surgery) or
tuberculosis in women from certain geographical locales. All
work through the formation of scar tissue inside the uterus.
2. Idiopathic: no prior cause is identified.
Evaluation of The Uterine Cavity
Proper evaluation of the uterine cavity and lining is an
integral component of fertility evaluation and monitoring is
also essential during treatment. Methods of evaluation include
i. Vaginal ultrasound for the thickness and pattern during the
follicular and luteal phases of the menstrual cycle
ii. Evaluation of the cavity of the uterus using HSG
(hysterosalpingogram), saline sonography (water sonogram) or
hysteroscopy. Saline sonography is the most invasive and is a
very accurate method for evaluation of the cavity and identify
if a lesion arising from the wall of the uterus projects into
the cavity.
iii. MRI: magnetic resonance imaging can accurately identify
abnormalities in the wall of the uterus; fibroids,
adenomyosis, congenital anomalies (septum, bicornuate, T shape
uterus)
iii. Endometrial biopsy: rarely indicated. The lining of the
uterus is sampled and with special stain to detect chronic
infection. The value of this testis questionable.
Treatment of Abnormal Endometrial Lining
Many treatments are available to normalize the cavity of the
uterus and improve the lining
1. Excision of hydrosalpinx: a dilated blocked fallopian tube
especially those seen on ultrasound should be excised to avoid
leak of fluid into the uterus. This has the potential of
doubling the implantation rate of embryos. Laparoscopy can be
used to remove dilated tubes in a minimal access day surery
2. Asherman syndrome: operative hysteroscope can be used to
accurately cut the scar tissue and allow the surrounding
healthy lining to cove the row area. The lining is treated
with estrogen after surgery to promote healing
3. Uterine fibroids and polyps and spetum can be removed using
operative hysteroscope.
4. Antibioitics to treat chronic inflammation of the lining of
the uterus are seldom effective.
5. During IVF if the lining is not favorable all embryos can
be frozen. In subsequent cycle, the lining is prepared with
estrogen as long as needed till adequate thickness and pattern
is achieved. Progesterone is then started and embryos are
thawed in the appropriate time and transferred into the
uterus.
6. Sildenafil (viagra) can be given as vaginal tablets but its
value is questionable.
7. Gestational carriers can be used if all other methods fail.
Meticulous attention to the condition of the lining and cavity
of the uterus is important during fertility treatment of the
uterus. Endoscopic surgery and hormone preparation can improve
the majority of the linings and increase the chance for embryo
implantation
Idiopathic
Infertility
Treatment: what do you need
to know
Idiopathic Infertility Treatment:
what do you need to know
Idiopathic infertility (unexplained infertility) is defined as
inability to conceive after trying for 6 months in women 35y
or older and one year for women younger than 35, with no
tubal, ovarian or male factor infertility. This diagnosis of
idiopathic infertility is established after open fallopian
tubes are detected in HSG or laparoscopy, regular ovulation is
detected from history, lab tests and ultrasound and sperm is
near normal on sperm analysis. These fertility tests can be
performed within few days. Note that good health and physical
fitness..etc are not factors here. Many women with terrible
general health do conceive. On the other hand, many women in
excellent physical fitness and sound health have extreme
difficulty conceiving even with fertility treatment. Having
difficulty getting pregnant without an apparent cause applies
to a large category of the sub-fertile population and is
puzzling to couples trying to conceive. The consensus of
opinion among reproductive endocrinologist can divide the
underlying factors for unexplained infertility into
1. Chromosomal abnormalities in the egg (low egg
quality)
Abnormal eggs are present in every woman, albeit to a varying
degree. Older women has more abnormal eggs. In addition, the
fewer eggs you have the higher the proportion of abnormal
eggs. There is no non-invasive test for egg quality and
history, age, blood tests for ovarian reserve and antral
follicle count detected on vaginal ultrasound are the most
used methods.
Factors that point to low egg quality
1. Advanced maternal age,
2. Diminished ovarian reserve (e.g high FSH, low AMH), also
prior surgery in the ovaries, smoking, family history of
early menopause and exposure to chemotherapy
3. Early pregnancy loss before a fetal heart activity is
detected (chemical pregnancy, blighted ovum),
4. Abnormal chromosomes of the products of conception and
5. Abnormal chromosome configuration of male or female
partner e.g chromosome translocation. Less than 5% of
couples miscarry due to a translocation in the male or
female partner.
2. Other factors: may be more prevalent in younger patient and
include mild endometriosis, immunological factors as antisperm antibodies, abnormality in cervical mucus, abnormalities
in the cavity of the uterus and endometrial lining. Generally,
these are not considered major factors in idiopathic
infertility. Mostly oral medication produce few or only one
follicles, thus they do not increase te chance that one or
more eggs are healthy leading to a pregnancy.
Treatment
Options
Infertility
for
Idiopathic
Oral medication – IUI or expectant treatment
(intercourse)
Oral medications are either clomid (clomiphen citrate) or an
aromatase inhibitor (mostly letrozole) are used. This is
followed by intercourse or intrauterine insemination (IUI).
The pregnancy rate is about 5% to 7% per treatment cycle.
There is no evidence that oral medications followed by IUI are
superior to just intercourse in treatment of unexplained
infertility. The risk for multiple pregnancy is about 8%.
However, because oral medication (clomid) widespread use,
mostly without ultrasound monitoring, they are probably
responsible for more multiple pregnancy than any other
fertility treatment.
Injection medications – IUI
This treatment should probably be avoided in the majority of
couples because of a. No added benefit: Pregnancy rate is not
significantly higher than Clomid-IUI cycles; 9% pregnancy rate
per treatment cycle and drops to 5% in women >38y. b. Risks:
notably multiple pregnancy (two or more babies; 30%) and
higher order multiple pregnancy (three or more babies; 3 to
8%). Multiple pregnancy has significant risks to the mother
and babies. Preterm delivery can be associated with permanent
neurological and intellectual defects in the babies. This risk
can be minimized with careful stimulation under supervision of
a reproductive endocrinologist, but cannot be completely
prevented.
In Vitro Fertilization (IVF)
a. The pregnancy rate per an IVF treatment cycle is
approximately 30% on average, three times that of IUI. The
specific pregnancy rate is dependent on female age. The time
to conception is also shorter than any other fertility
treatment modality. The higher success rate can be further
extended through the use of frozen embryos in couples that
have good quality embryos available for freezing. The
cumulative pregnancies resulting from fresh transfer and
subsequent frozen-thaw embryo transfer can result in a very
high odds for pregnancy. Frozen embryos can be used years
after their creation, when ovarian reserve has considerably
diminished. The contribution of IVF to treatment success
becomes more pronounced in older women >38 years as the
success of ovarian stimulation – IUI drops considerably. b.
The risk for twins and higher order multiple pregnancy can be
greatly minimized through single embryo transfer (1% twins and
no higher order multiple pregnancy). In other words if you
want to get pregnant faster, with one baby and at higher
chance for success per treatment cycle strongly consider IVF
with single embryo transfer.
Infertility Treatment Strategy for Idiopathic
Infertility
Conventional fertility treatment: “expectant management →
clomid / letrozole- IUI x2 to 3 cycles ‍→ gonadotropin – IUI
x3 cycles → IVF ” is the old method of treatment for
unexplained infertility Modern treatment of Unexplained
infertility: ” expectant management or oral medication – IUI →
IVF preferably with single embryo transfer “. Women 38 years
and older modern treatment strategy suggests Immediate IVF as
the initial fertility treatment. The modern paradigm for
fertility treatment will lead to pregnancy faster, is more
successful, minimize multiple pregnancy and is more cost
effective (lower dollar cost per baby). The majority of women
(>70%) with unexplained infertility especially women with
normal ovarian reserve will succeed in delivering a baby.
Letrozole
vs
Clomid
for
Ovulation Induction in PCOS
Letrozole vs Clomid
Induction in PCOS
for
Ovulation
Polycystic Ovary Syndrome (PCOS) is associated
with two of the following criteria:
a. No ovulation (anovulation) or less frequent ovulation
b. Hign male hormone (androgen)
c. Polycystic appearance of the ovaries: large number of small
follicles
Clomid is an oral medication that modulate or mask
the estrogen receptor leading to release of
internal FSH from the brain
Polycystic Ovary
Letrozole is an oral medicine that reduces
estrogen production from the ovary through
antagonizing the function of the aromatase enzyme,
responsible for making estrogen. The brain respond
by releasing FSH.
Which one is better?
In a recent good quality study, 750 infertile women, aged of
18-39 years, with a diagnosis of PCOS were studied. The women
were randomly allocated to CC vs. letrozole for 5 treatment
cycles. CC 50mg every day for 5 days (days 3-7 of cycle), or
B) letrozole 2.5mg every day for 5 days (days 3-7 of cycle),
for a total of 5 cycles or 25 weeks. The dose will be
increased in subsequent cycles in both treatment groups for
non-response or poor ovulatory response up to a maximum of 150
mg of CC a day (×5 days) or 7.5mg of letrozole a day (×5
days). 27.5% of women who received letrozole (Femara) had a
live birth, compared with 19.5% of women treated with
clomiphene. One quarter were clomid resistant and never
ovulated.
Letrozole was associated with lower multiple pregnancy rates.
Letrozole appears to improve live birth and pregnancy rates in
subfertile women with anovulatory PCOS, compared to clomiphene
citrate.
Letrozole should be considered as a first line agent for
induction of ovulation in women diagnosed with PCOS.
In general it is adviced that oral medication are tried first
in PCOS before proceeding to injection medications
(gonadotropins). Gonadotropins induce multiple ovulation and
increase the risk for multiple pregnancy. If oral medications
fail to induce ovulation or no pregnancy ensues, it is
preferable to proceed to IVF with single embryo transfer and
not injectable medications – IUI to avoid twins and higher
order multiple pegnancy.
Asian
Women
Problems
&
Fertility
Asian Women & Fertility Problems
Majority of Asian Women and Men agree that it is very
important for them to have children. Unfortunately, many Asian
couples face challenge trying to conceive naturally or using
fertility treatment. The decline in natural fertility and the
lower success of IUI and IVF in Asian women is documented in
The US, UK, China, Japan, Korea and other Asian countries.
Fertility in Asian countries has declined to the population
replacement rate 2.1 or lower. Many factors contribute to
decline in natural fertility in Asian women;
Ovarian Reserve in Asian Women
When compared to Caucasian women, Asian women undergoing IVF
significantly produce less eggs at all Anti-Mullerian hormone
(AMH) levels, even in women with high AMH. AMH is the most
accurate marker for ovarian reserve.
Gynecologic and medical disorders that impairs fertility:
PCOS, endometriosis and Systemic lupus (SLE) are more common
in Asian women.
Vaginismus : may interfere with regular intercourse in some
Asian women.
Environmental Factors: Asian women has more exposure to methyl
Mercury and vitamin D deficiency.
Culture : surveys of Asian women and men indicate that they
are less likely to consent to be contacted for fertility
research, are fatalistic about failure to conceive, less
informed about fertility issues, only 36 percent knew that
chances of getting pregnant declined with age, and are less
likely to suspect a male factor.
Asian women are commonly late at seeking care for infertility
and overestimate the chance for getting pregnant.
Genetics : Many genes are likely involved. FMR1 is a gene on X
chromosome responsible for Fragile X syndrome and its
variants. High repeats at this gene may reduce ovarian
reserve.
Fertility Treatment Outcomes in Asian
Couples
1. Pregnancy and delivery rates are lower in Asian women
following ovarian stimulation and IUI compared to white
women
2. IVF: when compared to white women in the US, 31 per
cent of the Asian women gave birth successfully compared
to 48 per cent of the white women. Asian women were also
less likely to become pregnant; 43 percent against 59
per cent even after control for many fertility factors.
Enodmetrial lining was thinner in Asian women compared
to Caucasian women.
Asian women should be aware that fertility treatment may be
less successful and seek care of a reproductive
endocrinologist and fertility specialist as early as possible.
In addition there are other factors that require attention in
Asian women during fertility treatment especially the higher
prevalence of chronic hepatitis B infection.
After conception, asian women at are a higher risk for
gestational diabetes.
What do Millennial women
think about infertility?
What
do
Millennial
women
think
about infertility?
Millennial generation were borne between 1982 and 2000. They
have commonalities not shared by other generations. Generation
Y is the highest-educated generation in American history.
On the Incidence of infertility in the US
The 2006–2010 National Survey of Family Growth (NSFG),
indicates that the incidence of infertility among married
women aged 15–44 is 6.0% (1.5 million) in 2006–2010, down from
8.5% in 1982 (2.4 Million women).
Impaired Fecundity (ability to have a live birth) among
married women aged 15–44 Increased from 11% In 1982 To 15% In
2002, But decreased to 12% In 2006–2010. Both Infertility and
impaired fecundity remain closely associated with age. The
decline is probably reflects greater delay in childbearing
(less women attempt to conceive thus less fit the definition
of infertility).
Infertility prevalence can be estimated using two approaches:
[1] a constructed measure derived from questions on sexual
activity, contraception, relationship status, and pregnancy,
and [2] a measure based on estimated time to pregnancy derived
from the respondents’ current duration of pregnancy attempt
(i.e., current duration approach). Prevalence was
approximately twofold higher using the current duration
approach (15.5%) vs. the constructed measure (7.0%). Both
methods identified similar patterns of effect of increasing
age (American Society for Reproductive Medicine 2013).
On Delaying Marriage in Generation Y
According
51% of US
women are
women is
to Pew Research Center analysis of U.S. Census data,
adults are currently married. Only 22% of Millennial
married. The median age of first marriage for Gen Y
26.5 years and for men 28.7. Currently, there are
more unmarried women in their early 30s than at any time in
the last 60 years in the US.
Millennial Women : late marriage and
late first birth
Millenials give birth to their first child many years later
than predecessors. The mean age at first child’s birth for
women was 23 and the mean age at first child’s birth for men
was 25 and even much later in more recent research (The
Guttmacher Institute). One-half of first births to women were
in their 20s and two-thirds of first births were fathered by
men who were in their 20s. On average, women aged 15-44 have
1.3 children as of the time of the interview.
Delay in bearing a child remains true even after cohabitation
and other adult living arrangements are considered. The gap
between first sex and first birth is 9+ years for Gen Y and 3+
years for Gen X.
Millennial Women Overestimate
Fertility Potential
their
Many Generation Y women, age 25 to 35, think a 30 year old
woman has a 70-per cent chance of conceiving per month and in
a 40 year old is close to 60% (Fertility IQ 2011 Survey, 1,000
women). Women were wrong most often about how long it takes to
get pregnant and about how much fertility declines at various
ages.
It is not clear why do millennials overestimate their
fertility potenials possible explanations could be [1]
Ignoring the disconnect between general health and ovarian
aging; women can be very healthy and have very few eggs
remaining in the ovary.
[2] Media celebrated older high profile and celebrity births
in mid 40s.
[3] Some success of fertility treatment in older mothers.
Generation Y women are anxious about
their fertility
Perceived infertility is the individual’s belief that she or
he is unable to conceive or impregnate, regardless of whether
this belief is medically accurate. Overall, 19% of women
believed that they were very likely to be infertile, according
to a Gutmacher institute 2012 survey of 1,800 unmarried men
and women aged 18–29. A survey from Europe indicates that 31%
of women and 52% of men believe that dramatic decline of
fertility occurs after age 44.
On The Utilization of Fertility Services
by Millennial Women
Millennial women appear to utilize Fertility Service different
than generation X. Twelve percent of women aged 15-44 in
2006-2010 (7.3 million women), or their husbands or partners,
had ever used infertility services. Among women aged 25-44,
17% (6.9 million) had ever used any infertility service, a
significant decrease from 20% in 1995. Thirty-eight percent of
nulliparous women with current fertility problems in 2006-2010
had ever used infertility services, significantly less than
56% of such women in 1982. In all survey years, ever-use of
medical help to get pregnant was highest among older and
nulliparous women (NSFG). Gen Y also overestimate the success
rate of IVF.
Consideration of fertility by generation Y without changing
reproductive plans include
1. No harm in evaluation of ovarian reserve. Some women,
though very young, do have a diminished ovarian reserve
to the extent that delay of seeking fertility treatment
is detrimental to there ability to conceiving a
biological child
2. Delaying childbearing does not mean ignoring fertility
for an undefined period. Many options can be exercised
to
preserve
fertility,
including
lifestyle
modifications, egg freezing and embryo freezing.
Preconception Checklist
Preconception Checklist
What should you do if you decided
to get pregnant?
Start prenatal vitamins : one tablet per day. Make sure that
It contains 1mg of folic acid and has 5000 units (not more)
of vitamin A
Visit your gynecologist : for
vaccination history.
history, exam, pap test and
Preconception labs : to assess the safety of pregnancy. Tests
should include hepatitis B surface antigen, hepatitis C
antibody, HIV, blood type, blood count, prolactin, TSH
(thyroid function), cultures for gonorrhea and Chlamydia.
Genetic screening : to assess the carrier state of the parents
for common genetic diseases and the risk for transmission to
children. Basic tests include common mutation for cystic
fibrosis, spinal muscular atrophy and fragile X syndrome.
Additional tests are related to ethnicity: hemoglobin
abnormalities in blacks, Mediterraneans and Asians, Ashkenazi
profile for European Jews, Tay Sach disease for Jews and
French Canadians. Another approach is to apply a ‘universal
genetic test’ that encompasses a large number of genetic
mutations for many diseases irrespective of ethnicity to allow
for detection of rarer genetic diseases or even to sequence
the whole genes related to theses diseases.
Lifestyle factors : better nutrition e.g one serving of small
fish per week , stop smoking, avoid alcohol and reduce
exercise if doing strenuous training
Worried? have a risk factor? or wants a more proactive
approach?: Obtain a sperm analysis, HSG to test if the tubes
are open and ovarian reserve tests to investigate the function
of the ovaries (vaginal ultrasound and blood work).
Intercourse: have regular intercourse three times a week
without attempting to monitor or to time ovulation.
For How Long should you try to conceive
before moving to the next step?
a. If a fertility factor known or detected e.g abnormal sperm
analysis, blocked fallopian tube, no ovulation, low ovarian
reserve, carrier of genetic mutation… you should seek
consultation with a reproductive endocrinologist
b. If no fertility factor is known:
1. Female age < 35 years try to conceive for one year before
seeking consultation with a reproductive endocrinologist
2. Female age ≥ 35 years seek consultation within 6 months if
not pregnant